Viscoelastic Mass Research Articles

Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 2: Experimental validation of the models of expansion, post-expansion mechanical strength, and drug release

In Part 1, we have introduced expandable gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. The expansion rate, post-expansion mechanical strength, and drug release rate were modeled for a dosage form containing 200 mg nilotinib. In the present part, the dosage form was prepared and tested in vitro to validate the models. Upon immersing in a dissolution fluid, the fibrous dosage form expanded at a constant rate to a normalized radial expansion of 0.5 by 4 h, and then formed an expanded viscoelastic mass of high strength. The drug was released at a constant rate over a day. For comparison, a particle-filled gelatin capsule with the same amount of nilotinib disintegrated almost immediately, and released eighty percent of the drug content in just 10 min. The experimental data validate the theoretical models of Part 1 reasonably

Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 1: Dosage form design, and models of expansion, post-expansion mechanical strength, and drug release

At present, the efficacy and safety of many sparingly-soluble tyrosine kinase inhibitors (TKIs) delivered by the prevalent oral dosage forms are compromised by excessive fluctuations in the drug concentration in blood. To mitigate this limitation, in this four-part study gastroretentive fibrous dosage forms that deliver drug into the gastric fluid (and into the blood) at a controlled rate for prolonged time are presented. The dosage form comprises a cross-ply structure of expandable, water-absorbing, high-molecular-weight hydroxypropyl methylcellulose (HPMC)-based fibers coated with a strengthening, enteric excipient. The intervening spaces between the coated fibers are solid annuli of drug particles, and low-molecular-weight HPMC and enteric excipients. The central regions of the annuli are open channels. In this part, models are developed for dosage form expansion, post-expansion mechanical strength, and drug release. The models suggest that upon immersing in a dissolution fluid, the fluid percolates the open channels, diffuses into the annuli and the coated fibers, and the dosage form expands. The expansion rate is inversely proportional, and the post-expansion mechanical strength proportional to the thickness of the strengthening coating. Drug particles are released from the annuli as the surrounding excipient dissolves. The drug release rate is proportional to the concentration of low-molecular-weight HPMC at the annulus/dissolution fluid interface. The dosage forms can be readily designed for expansion in a few hours, formation of a high-strength viscoelastic mass, and drug release at a constant rate over a day.

In situ studies of plant-based meat analog texturization

Plant-based meat analogs are the rising stars of the food industry as they promise to mimic the experience of eating meat without killing animals. They are popular due to their meat-like fibrous structures and typically obtained via high-moisture extrusion cooking. Texturization is believed to mainly take place during the solidification in a cooling die attached to the end of the extruder. However, the mechanisms behind this texturization are not fully elucidated yet. This work presents in situ studies of fiber evolution within a custom-designed extruder cooling die by small-angle neutron scattering on a length scale from 1.3 to 436 nm. The measurements demonstrated that macroscopic fibrous structures did not emerge from unfolding, elongation and orientation on molecular level. This contradicts existing hypothesis of the structuring mechanism underlying the meat-like fibers. Instead, the scattering patterns indicate the presence of densely packed protein nano-aggregates of around 40 nm consisting of globular proteins with a diameter of 9 nm. Based on that, chain-like arrangement of protein nano-aggregates, fractures of the viscoelastic mass in the flow field and sharp temperature-dependent solidification are proposed as underlying mechanisms for macroscopic fiber formation.

WITHDRAWN: Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 1: Dosage form design, and models of expansion, post-expansion mechanical strength, and drug release

At present, the efficacy and safety of many sparingly soluble tyrosine kinase inhibitors (TKIs) are compromised due to the drug's pH-dependent solubility, and the associated excessive fluctuations in the drug concentration in blood. To mitigate this limitation, in this four-part study gastroretentive fibrous dosage forms that deliver drug into the low-pH gastric fluid (and into the blood) for prolonged time are presented. The dosage form comprises a cross-ply fibrous structure of water-absorbing, high-molecular-weight hydroxypropyl methylcellulose (HPMC) fibers coated with a strengthening, enteric excipient. The intervening spaces between the coated fibers are solid annuli that contain drug particles, low-molecular-weight HPMC, and an enteric excipient. There are open channels in the central regions of the annuli. In this first part, models are developed for in vitro dosage form expansion, post-expansion mechanical strength, and drug release. The models suggest that the expansion rate and the post-expansion mechanical strength can be varied by changing the thickness of the enteric coating over the fibers. The drug particles in the annulus are released as the surrounding excipient erodes. The drug release rate is proportional to the concentration of low-molecular-weight HPMC at the interface between the annulus and the dissolution fluid in the channels. The dosage forms can be readily tailored for expansion in a few hours, formation of a high-strength viscoelastic mass, and drug release at a constant rate over a day.

WITHDRAWN: Gastroretentive fibrous dosage forms for prolonged delivery of sparingly soluble tyrosine kinase inhibitors. Part 2: Experimental validation of the models of expansion, mechanical strength, and in vitro drug release

In Part 1, we have introduced gastroretentive fibrous dosage forms with expandable, strengthened excipient fibers, and drug-loaded inter-fiber space for prolonged delivery of sparingly soluble tyrosine kinase inhibitors. The in vitro expansion rate, post-expansion mechanical strength, and drug release rate were modeled for a dosage form containing 200 mg of nilotinib. In the present part, the dosage form was prepared and tested in vitro to validate the models. Upon immersing in a dissolution fluid, the fibrous dosage form expanded at a constant rate to a normalized radial expansion of 0.5 by 4 h, and then formed an expanded viscoelastic mass of high strength. The drug was released at a constant rate over a day. For comparison, a particle-filled gelatin capsule with the same amount of nilotinib disintegrated almost immediately, and released eighty percent of the drug content in just 10 min. The data validate the models of Part 1.

The optimum inerter-based additional viscoelastic mass dampers for dynamic response mitigation of structures

The additional inerter-based viscoelastic mass dampers (AIVMD) and additional viscoelastic mass damper inerters (AVMDI) are introduced in this article. H 2 and H ∞ optimization schemes are utilized to derive the optimal closed-form solutions for these novel dampers analytically. A parametric study performs to investigate the sensitivity of the optimal design parameters with other system parameters such as damper mass ratio, inerter mass ratio, and stiffness ratio. Thus, a higher damper mass ratio, a higher inerter mass ratio, and a higher stiffness ratio are recommended to design optimum novel dampers for achieving robust vibration reduction capacities. Therefore, H 2 optimized AIVMD and AVMDI have 53.23 % and 57.73 % dynamic response reduction capacities while H ∞ optimized AIVMD and AVMDI can provide 72.97 % and 75.57 % dynamic response reduction capacities subjected to harmonic excitation, respectively. In addition, random-white noise excitations are also applied instead of harmonic excitation to cross-check the accuracy of the optimal design parameters. The overall result shows that 74.24 % and 82.17 % dynamic response reduction capacities for H 2 optimized AIVMD and AVMDI, furthermore, 92.14 % and 94.36% dynamic response reduction capacities for H ∞ optimized AIVMD and AVMDI. These optimal closed-form solutions are mathematically accurate and relevant for practical applications.

Modification of zein dough functionality using kafirin as a coprotein

Kafirin, sorghum prolamin, was investigated as a coprotein for zein as visco-elastic masses and in starch-based model doughs. Regular kafirin and kafirins from waxy and high protein digestibility (HD) sorghum crosses were studied. HPLC revealed that waxy-HD kafirin was of smaller molecular size and low in β-kafirin. It also had greater surface hydrophobicity. Kafirin addition to zein increased visco-elastic mass elasticity up to ≈50% stress-recovery, similar to wheat gluten. Waxy-HD kafirin gave the highest elasticity, possibly due to its hydrophobicity. Kafirin inclusion at 2:8 parts zein increased the tensile strength of model doughs. Maximum strength was, however, only 60% that of gluten-based dough. Kafirin from regular sorghum gave the highest strength, possibly because of greater disulphide-bonded polymerisation. Confocal laser scanning microscopy showed that zein-kafirin copolymers formed fairly linear fibrils in stretched doughs, indicating excellent compatibility between the proteins. Future research should establish how kafirin-zein copolymer performs in non-wheat flour products.

Development of Multi-Directional Dynamic Vibration Absorber Composed of Cubic Viscoelastic Bodies and Mass

Development of Multi-Directional Dynamic Vibration Absorber Composed of Cubic Viscoelastic Bodies and Mass

Laboratory testing of static and dynamic deformation characteristics of small scale model of pavement subgrade

Interaction system vehicle-pavement represents actual problem in terms of structural, life service and environmental requirements. Experimental measurements with real vehicles and pavements are time consuming and bring high complexity of the inputs, relations and other boundary conditions which need to be identified to achieve reliable outputs. Inevitable uncertainties related to the real structure can be controlled when scale models with identified boundary conditions are prepared. Determination of the characteristics of the individual components of the vehicle-pavement interaction system at controlled conditions is then possible. The subgrade is an important part of the pavement structure. A laboratory and numerical simulations based on the static and dynamic testing methods were used to determine the deformation parameters of the subgrade. A viscoelastic mass was selected as a subgrade for the small scale model of the pavement. Its characteristic allows the simulation of the dynamic effects of the vehicle on pavement structure. A short-time dynamic loading of the subgrade occurs when the vehicle moves on the pavement. Therefore, the response of the subgrade should be also characterized with the dynamic parameters. The results obtained by the experimental observations in-lab will be used for the evaluation of the traffic effect on the pavement structure and surrounding objects such as buildings.

Influence of dough sheeting, flour pre-gelatinization and zein inclusion on maize bread dough functionality

Developing tropical countries need simple technologies to enable the production of bread from locally produced cereals, such as maize and sorghum. However, current gluten-free bread making technology relies heavily on the addition of additives, which results in products that are nutritionally inferior to wheat breads. Hence, this study investigated the technologies of flour pre-gelatinization and dough sheeting plus addition of commercial zein to improve maize dough functionality and bread quality. A strong and cohesive maize flour dough could be produced as a result of uniform incorporation of a 30% of pre-gelatinized maize flour through repeated dough sheeting. Pre-gelatinized starch acts as a hydrocolloid and the dough viscosity was probably increased through the hydroxyl groups of the hydrocolloidal structure enabling more interactions with water molecules. The dough still lacked extensibility. However, extensibility and gas-holding were significantly improved by additionally incorporating an α-zein viscoelastic mass above its glass transition temperature into the dough during sheeting. The zein fibrils appeared to entrap the maize flour particles. Zein inclusion also improved bread crumb cell structure and increased loaf volume somewhat. However, the crumb cell walls were much thicker than in wheat bread and comprised clumps of starch granules.

A time-domain recursive method of SH-wave propagation through the filled fracture with linear viscoelastic deformation behavior

ABSTRACT The study of SH-wave across fractures can help uncover and improve the understanding of seismic wave propagation across geological media with fractures. Considering the viscoelastic behavior of a filled medium, a time-domain recursive method of SH-wave propagation through filled viscoelastic fractures was established. A displacement and stress discontinuous model and a differential constitutive relationship of the viscoelastic model were adopted to describe viscoelastic deformation behavior and mass of filled medium in fractures. Three viscoelastic models were utilized to analyze the effects of different viscoelastic models on wave propagation. The effects of frequency, incident angle, specific stiffness, and specific viscosity on the transmission and reflection coefficients and energy dissipation rate were discussed. Also, the influence of fracture slip behavior and the effects of filling mass on wave propagation were also addressed and the results indicated that the method established here was effective for investigating the propagation of SH-wave across viscoelastic filled fractures. Viscosity coupling might have caused a phase delay when the wave stress reached the shear strength and the filling mass had a subtle influence on SH-wave propagation through filled fractures with a thinner interlayer.

Formation of lycopene-loaded hydrolysed collagen particles by supercritical impregnation

This work aimed to study the formation of lycopene-loaded hydrolysed collagen (LLHC) particles by supercritical CO2 impregnation. For this, a mixture of 9.09 g of hydrolysed collagen powder and 0.91 g of lycopene was placed in an autoclave for contact with supercritical CO2 at pressures of 150 and 250 bar, and temperatures of 50 and 60 °C, with agitation at 1250 rpm for 45 min. At 60 °C (150 and 250 bar), the mixture became a viscoelastic mass. At 50 °C (150 and 250 bar), lycopene was loaded into the physical structure of the hydrolysed collagen powder particles. LLHC particles formed at 150 bar and 50 °C, when compared to 250 bar and 50 °C, showed fissures on their surface, which enabled possible electrostatic interactions and better impregnation and distribution of lycopene. Thus, supercritical CO2 impregnation at 150 bar and 50 °C is recommended for the formation of LLHC particles.

Near/far side asymmetry in the tidally heated Moon

Using viscoelastic mass spring model simulations to track heat distribution inside a tidally perturbed body, we measure the near/far side asymmetry of heating in the crust of a spin synchronous Moon in eccentric orbit about the Earth. With the young Moon within ≲8 Earth radii of the Earth, we find that tidal heating per unit area in a lunar crustal shell is asymmetric due to the octupole order moment in the Earth's tidal field and is 10 to 20% higher on its near side than on its far side. Tidal heating reduces the crustal basal heat flux and the rate of magma ocean crystallization. Assuming that the local crustal growth rate depends on the local basal heat flux and the distribution of tidal heating in latitude and longitude, a heat conductivity model illustrates that a moderately asymmetric and growing lunar crust could maintain its near/far side thickness asymmetry but only while the Moon is near the Earth.

Comparative functional properties of kafirin and zein viscoelastic masses formed by simple coacervation at different acetic acid and protein concentrations

Kafirin and zein could be used in making wheat-free leavened dough-based products if their functionality can be modified to more closely resemble gluten. Recently, stable viscoelastic masses were produced from isolated kafirin and total zein by dissolution of the prolamins in glacial acetic acid, followed by simple coacervation with rapid water addition. The methodology was, however, not compatible with food systems, as the final acid concentration was too high (33%). This work revealed that coacervation with reduction in the final acetic acid concentration down to 0.1% still enabled formation of kafirin and zein viscoelastic masses, with functionality retained on storage at 4 °C for an extended period; indicating an irreversible molecular change with dissolution in glacial acetic acid. Kafirin masses were much firmer than zein masses but both were softer than gluten. However, kafirin displayed a similarly elastic high component to gluten, whereas zein exhibited more viscous flow characteristics. This was probably due to the presence of more disulphide bonds in kafirin than zein. A model to explain this behaviour is proposed. Regarding the effect of prolamin concentration in glacial acetic acid, a minimum, between 5 and 10% was necessary for viscoelastic mass formation at low final acetic acid concentration (5%).

Integrating viscoelastic mass spring dampers into position-based dynamics to simulate soft tissue deformation in real time.

We propose a novel method to simulate soft tissue deformation for virtual surgery applications. The method considers the mechanical properties of soft tissue, such as its viscoelasticity, nonlinearity and incompressibility; its speed, stability and accuracy also meet the requirements for a surgery simulator. Modifying the traditional equation for mass spring dampers (MSD) introduces nonlinearity and viscoelasticity into the calculation of elastic force. Then, the elastic force is used in the constraint projection step for naturally reducing constraint potential. The node position is enforced by the combined spring force and constraint conservative force through Newton's second law. We conduct a comparison study of conventional MSD and position-based dynamics for our new integrating method. Our approach enables stable, fast and large step simulation by freely controlling visual effects based on nonlinearity, viscoelasticity and incompressibility. We implement a laparoscopic cholecystectomy simulator to demonstrate the practicality of our method, in which liver and gallbladder deformation can be simulated in real time. Our method is an appropriate choice for the development of real-time virtual surgery applications.

Comparison of formation of visco-elastic masses and their properties between zeins and kafirins

Zeins of differing sub-class composition much more readily formed visco-elastic masses in water or acetic acid solutions than equivalent kafirin preparations. Visco-elastic masses could be formed from both zein and kafirin preparations by coacervation from glacial acetic acid. Dissolving the prolamins in glacial acetic acid apparently enabled protonation and complete solvation. Stress-relaxation analysis of coacervated zein and kafirin visco-elastic masses showed they were initially soft. With storage, they became much firmer. Zein masses exhibited predominantly viscous flow properties, whereas kafirin masses were more elastic. The γ-sub-class is apparently necessary for the retention of visco-elastic mass softness with kafirin and zein, and for elastic recovery of kafirin. Generally, regardless of water or acetic acid treatment, all the zein preparations had similar FTIR spectra, with greater α-helical conformation, than the kafirin preparations which were also similar to each other. Kafirin visco-elastic masses have a much higher elastic character than zein masses.

Formation and properties of viscoelastic masses made from kafirin by a process of simple coacervation from solution in glacial acetic acid using water

Stable viscoelastic masses have been formed from kafirin in a mainly aqueous system. Kafirin was dissolved in glacial acetic acid (GAA) and simple coacervation was performed by rapid addition of 15°C water under low shear. Kafirin precipitated out as a network of hydrated fibrils which could be hand-kneaded into a viscoelastic mass. These could be formed from a very wide range of kafirins, including those where β- or γ-subclass expression was suppressed. Kafirin composition influenced the appearance of the masses but did not fundamentally affect stress-relaxation behaviour. Fresh kafirin masses exhibited similar elasticity and viscous flow balance to gluten. They maintained functionality when stored for several days at 10°C but their elastic component increased. FTIR showed that when kafirin was dissolved in GAA its α-helical conformation increased substantially. Dissociation of the kafirin molecules in GAA, assuming a α-helical conformation may have enhanced water binding, enabling viscoelastic mass formation.

Three-Dimensional Modeling of Circulating Cell Separation in a Y-Junction Microchannel

The migration of living cells plays an important role in immune response, cancer progression, and microfluidic technologies for cell separation and flow cytometry that often involve bifurcating (e.g., Y-or T-shaped junction) microchannels. Vessel bifurcations are among the frequent sites affected by atherosclerosis and are the focal points of drug carrier particle adhesion in vivo. Using VECAM, our custom three-dimensional computational algorithm for multiphase viscoelastic flow and mass transport, this study focuses upon the investigation of the effects of cell viscoelasticity and hydrodynamic interaction on separation of circulating cells in Y-shaped microchannels with angle ranging from 30° to 150°. In VECAM, the cell is modeled as a one-phase viscoelastic fluid material composed of a cytosol and a polymer (cytoskeletal) matrix. The cell viscoelasticity is described by the Giesekus constitutive equation. The cell-fluid interface is tracked by the volume-of-fluid (VOF) method, with the interfacial (cortical) tension force calculated by the continuous surface force (CSF) method. In the simulation, we consider single or two cells of initially spherical shape with the same or varying diameter. The separation of the cells has been investigated for different initial locations of the cells with respect to one another. The results of this study provide the critical conditions for cell separation including the critical values of cell diameter, elasticity, surface tension and initial cell-to-cell separation distances for a range of bifurcation angles. These critical conditions are important for the development of microfluidic devices to be optimized for separation and sorting of circulating cells and for understanding how circulating cells are separated in bifurcating microvessels.

Quartz crystal microbalance with microfluidic multi-stream solution control for mineralization kinetic analysis

We present a quartz crystal microbalance (QCM) sensor integrated with microfluidic multi-stream solution control for a variety of analysis applications, including improved studies of mineralization kinetics. The cost-effective assembly of this device and functionality of the QCM crystal in situations of rigid and viscoelastic mass loading are demonstrated. The significant advantage of this system is the control of solution mixing on-chip through the use of laminar parallel-flow which creates a liquid–liquid reaction interface at the QCM sensor. This shows improved sensor response times, due to laminar flow, of 105Hz/min compared to 19Hz/min for turbulent mixing in a bulk solution flow cell. This device adds to the current real-time mass measurements obtained from traditional QCM by allowing for simultaneous optical microscopy. The combination of QCM mass analysis, optical microscopy, and laminar parallel-flow to achieve a liquid–liquid reaction interface provides an analytical system well suited for the study of controlled mineralization. The microfluidic solution flow decreases non-specific mineralization and offers significant experimental control.

A fractional order controller for seismic mitigation of structures equipped with viscoelastic mass dampers

In this paper a fractional order (FO) controller is proposed for solving the vibration suppression problem in civil structures. A laboratory scaled steel structure, with one floor, modeled as a single degree-of-freedom system is used as a case study. Two passive control solutions are proposed: a tuned mass damper (TMD) and a viscoelastic damper (VED), the latter being modeled using fractional derivatives. The simulation results show that the VED is able to further reduce the vibrations induced as forced oscillations or due to seismic excitation inputs, as compared to the passive TMD. The FO controller is then tuned using a new approach based on imposing a magnitude condition for the closed-loop system at the structural resonance frequency. The resulting FO active control strategy, together with the VED, ensures an increased seismic mitigation. Structural modeling errors are also considered, with the proposed active FO control strategy behaving robustly in terms of vibration suppression. The novelty of the paper resides in the tuning approach, as well as in the proposed active control strategy that is based upon combing VEDs, described using an FO model, and an FO controller.